Molecular and cellular imaging, together with visualization of the tissue morphology and composition, can be used to distinguish vulnerable plaques and to aid in treatment of high risk atherosclerotic plaques. This project is focused on development of a new imaging agent - dye-loaded targeted liposomes, for detection of activated microphages in atherosclerotic plaques. We will synthetize liposomes loaded with a high concentration of ICG (FDA approved dye); the dye will form J-aggregates inside the liposomes with a high absorbance at 800 and 900 nm that will allow imaging in the presence of blood. The liposomes will be targeted to a biomarker of activated macrophages in vulnerable plaques: folate receptor beta (FR~). The targeted liposomes will accumulate in a plaque through areas of endothelial dysfunction and specifically interact with activated macrophages. The liposome-macrophage interactions will result in a profound change in the 800 to 900 nm peak ratio that will be quantified for visualization of the macrophages. After these studies, Phase II will be focused on scaling-up the liposome synthesis, studies relevant to regulatory filing, and large animal imaging studies. Given the biocompatible materials of dye-loaded liposomes and their broad applicability to multiple imaging modalities, we anticipate rapid clinical translation.